MM25: A phase 1b/II study of the efficacy of Venetoclax, Iberdomide and Dexamethasone (IberVenD) for patients in first or second relapse of Multiple Myeloma with t(11;14)
MM25: A phase 1b/II study of the efficacy of Venetoclax, Iberdomide and Dexamethasone (IberVenD) for patients in first or second relapse of Multiple Myeloma with t(11;14)
Australasian Leukaemia & Lymphoma Group
50 participants
Jul 19, 2023
Interventional
Conditions
Summary
This clinical trial aims to assess the effect of a combination therapy with Venetoclax, Iberdomide and Dexamethasone for the treatment of patients with first or second relapse of Multiple Myeloma t(11;14). Who is it for? You may be eligible for this study if you are aged 18 or older, you have been diagnosed with Multiple myeloma and have had 1-2 prior lines of treatment. Study details Participants who choose to participate in this trial will receive cycles of combination treatment. Each cycle is 28 days in length. The treatment is 3 products that will be used in combination. The first product, Venetoclax is an oral treatment and participants will take this from day 1 to day 28 of each cycle. The second product, Iberdomide is also an oral treatment and participants will take this from day 1 to day 21. The third product is Dexamethasone which participants have most likely had before. Dexamethasone will be taken on days 1, 8, 15 and 22. Participant will continue on the treatment combination until they are no longer responding to the therapy, or if the treatment causes too many adverse events. Safety assessments will be carried out by the Chief Investigator and trial committee. It is hoped this research will determine whether the combination of Venetoclax, Iberdomide and Dexamethasone is successful at treating people with relapsed or refractory multiple myeloma. If this combination treatment is found to be effective, it may be used to improve the health outcomes of future patients with refractory and relapsed multiple myeloma.
Eligibility
Inclusion Criteria18
- Males or females, age 18 years or older, capable of giving consent
- ECOG performance status of 0 to 2.
- Have confirmed MM as defined by IMWG criteria and have had 1 to 2 prior lines of therapy
- Have measurable disease defined by having at least one of the following:
- o Serum M-protein concentration of greater than or equal to 5g/L
- o Urine M-protein excretion of greater than or equal to 200mg/24 hours
- o Involved serum free light chain (SFLC) greater than or equal to 100mg/L and an abnormal SFLC ratio ( less than 0.26 or
- greater than 1.65)
- Positive for t(11;14) by fluorescence-in-situ-hybridisation (FISH) testing on bone marrow aspirate sample
- Adequate bone marrow function
- Adequate liver function (ALT/AST equal to 2.5 x Upper limit of normal, Bilirubin equal to 1.5 x Upper limit of normal)
- Adequate renal function (creatinine clearance equal to 30ml/minute)
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following applies
- o Is not a woman of childbearing potential (WOCBP) or
- o Is a WOCBP and is using a contraceptive method that is highly effective (with failure rate of less than 1%/year) during the study intervention and for at least 4 months after the last dose of the study drug
- A male participant is eligible to participate if they agree to refrain from donating sperm AND either agree to be abstinent from heterosexual intercourse or agree to use barrier contraception when engaging in sexual activity with a WOCBP (including pregnant females). This female partner must also be using an additional method of highly effective contraceptive method (with failure rate of less than 1%/year).
- Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments
- Signed, written informed consent
Exclusion Criteria19
- Previous treatment with Bcl-2 inhibitor or CELMod
- Any of the following conditions: Non-secretory Multiple Myeloma, solitary plasmacytoma or plasma cell leukaemia.
- Known Central nervous system involvement
- Systemic anti-myeloma therapy within less than or equal to 14 days with the exception of corticosteroids equivalent to dexamethasone less than or equal to 160mg in total within last 4 weeks.
- Major surgery within 14 days of initiating study treatment
- Radiotherapy within 14 days of initiating study treatment
- Female patients who are lactating or have a positive serum pregnancy test during screening period.
- Evidence of cardiovascular risk:
- o Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block;
- o History of myocardial infarction, acute coronary syndrome (including unstable angina), coronary angioplasty, or stenting or bypass grafting within the last 6 months;
- o Class III of IV heart failure defined by New York Heart Association functional classification system
- Known immediate or delayed hypersensitivity or allergy to previous drugs chemically related to venetoclax and/or Iberdomide.
- Acute infections requiring antibiotic, antifungal or antiviral therapy within 1 week prior to first dose.
- Known HIV infection.
- Hepatitis B surface antigen positivity or Hepatitis B DNA positivity at screening or within 3 months prior to first dose of study treatment. Participants with positive Hepatitis B core antibody testing can be enrolled if Hepatitis B DNA negative and receiving Hepatitis B prophylaxis.
- Known gastrointestinal disease or procedure that could interfere with the oral absorption or tolerance of iberdomide or venetoclax.
- Use of a strong or moderate CYP3A inhibitor or inducer within 1 week prior to starting first dose of study treatment.
- Diagnosed or treated for another malignancy within 2 years before study enrolment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
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Interventions
This is an adverse event-adaptive trial design for safety purposes. There will be intra-patient dose escalation over the first three cycles, i.e. all patients will start at ‘combination level 1’ during cycle 1, if there is no treatment-related Grade 3 neutropenia or Grade 4 thrombocytopenia, as per Common terminology criteria for adverse events version 6 (CTCAE v6), dose will be escalated to ‘combination level 2’ during cycle 2, then ‘combination level 3’ during cycle 3, respectively: • Cycle 1 (combination level 1)*: Iberdomide 1.3mg + Venetoclax 200mg • Cycle 2 (combination level 2): Iberdomide 1.3mg + Venetoclax 400mg • Cycle 3 onwards (combination level 3): Iberdomide 1.6mg + Venetoclax 400mg All patients will receive dexamethasone in each treatment combination level. *Note: In case of treatment related Grade 3 neutropenia or Grade 4 thrombocytopenia at ‘combination level 1’, then the dosing level will be deescalated to ‘combination level -1’: Iberdomide 1.0mg + Venetoclax 200mg. Dosing will be done on a 28-day cycle: - Venetoclax given orally from days 1-28 -Iberdomide given orally from days 1-21 -Dexamethasone given orally, 40mgs weekly (20mg for patients >75 years of age) Participants will continue on treatment until one of the following criteria applies: • Disease progression • Intercurrent illness that prevents further administration of treatment • Unacceptable AE(s) • Patient decides to withdraw from treatment or the study, or • General or specific changes in the patient's condition render the patient unacceptable for further treatment in the opinion of the investigator. Compliance will be monitored via drug accountability exercises completed by the participating site and the sponsor.
Locations(1)
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ACTRN12622001158752